Study to Investigate Safety and Response to 1 or 2 g Rectal Suppositories Containing 5 or 10 mg NRL001.

Randomised, Double-blind, Single Dose, Three-way, Cross-over Study to Investigate the Safety and Response to 1g or 2g Rectal Suppositories Containing 5 mg or 10 mg 1R,2S-methoxamine Hydrochloride [NRL001] or Matching Placebo

This is a healthy volunteer three-way crossover study. A total of 12 subjects will receive three single administrations of 1 g rectal suppositories (containing either 5 mg NRL001, 10 mg NRL001 or matching placebo), with a washout period of at least 7 days between dosings. A further 12 subjects will receive three single administrations of 2 g rectal suppositories (containing either 5 mg NRL001, 10 mg NRL001 or matching placebo), again with a 7 day washout period between dosings. The pharmacodynamic response, pharmacokinetics and safety profile will be determined.

Study Overview

• Status: Completed
• Conditions: Fecal Incontinence
• Intervention / Treatment: Drug: NRL001; Drug: NRL001

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG7 2UH
    • Department of GI Surgery, Nottingham University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. No previous history of ano-rectal conditions or diseases
2. No history of cardiovascular disease
3. 18 to 60 years of age
4. Males and females (pre-menopausal females of child-bearing potential must be using adequate contraceptive methods and have a negative pregnancy test before the start of the study)

Exclusion Criteria:

1. Use of medication in the last 30 days with a vasodilatory activity, or use of any medication currently or within the last 30 days which the Investigator believes may affect the study participation or results
2. Use of monoamine oxidase inhibitors presently or within the last 2 weeks before study participation
3. Use of any medication in the last 30 days applied to the anus and/or via the rectum
4. Application of any unlicensed medication within the previous 3 months or participation in any other research study in the last three months which involved being paid a disturbance allowance; having an invasive procedure (e.g. venepuncture >50ml, endoscopy) or exposure to ionising radiation.
5. Regular intake of more than 21 units of alcohol per week
6. History or any evidence of cardiovascular disease including ischaemic heart disease and hypertension (defined on examination: systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 90 mmHg; based on at least two separate readings), peripheral vascular disease or Raynaud's syndrome
7. Presence of diabetes mellitus
8. History or symptoms of thyroid diseases, including hypo- or hyperthyroidism
9. Pregnant or lactating females
10. History of any clinically relevant allergy
11. Presence of concomitant gastrointestinal diseases or disorders, such as significant abdominal symptoms and haemorrhoids but also any significant organ (e.g. renal, hepatic or cardiac) dysfunction
12. Volunteers whom the Investigator feels would not comply with the requirements of the trial
13. Volunteers who have been exposed to more than 5 mSv of ionising radiation in the last 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1 g suppository; Subjects receive 5 mg NRL001, 10 mg NRL001 and placebo in a 1g rectal suppository	Drug: NRL001; Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 1 g rectal suppository, with a 7-day washout period between dosing.; Drug: NRL001; Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository, with a 7-day washout period between dosing.
EXPERIMENTAL: 2 g suppository; Subjects receive 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository.	Drug: NRL001; Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 1 g rectal suppository, with a 7-day washout period between dosing.; Drug: NRL001; Subjects receive single doses of 5 mg NRL001, 10 mg NRL001 and placebo in a 2 g rectal suppository, with a 7-day washout period between dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in MARP after a single dose	6 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic plasma assessment to determine systemic uptake	6 hours
Adverse events	6 hours
Cardiovascular parameters; heart rate and blood pressure	6 hours

Collaborators and Investigators

• Sponsor: Norgine
• Investigators: Principal Investigator: John H Scholefield, MD, Nottingham University Hospital

Publications and helpful links

General Publications

• Simpson JA, Bush D, Gruss HJ, Jacobs A, Pediconi C, Scholefield JH. A randomised, controlled, crossover study to investigate the safety and response of 1R,2S-methoxamine hydrochloride (NRL001) on anal function in healthy volunteers. Colorectal Dis. 2014 Mar;16 Suppl 1:5-15. doi: 10.1111/codi.12541.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (ESTIMATE): March 6, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): December 23, 2009
• Last Update Submitted That Met QC Criteria: December 21, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Fecal Incontinence
• Other Study ID Numbers: NRL001-01/2008 (SUM)